The goal of the research plan is to characterize the intra-axonal protein interactions that lead to accelerated axonal outgrowth. When a conditioning nerve lesion precedes a testing lesion by a conditioning interval of two weeks, the rate at which daughter axons grow distally away from the testing lesion site is accelerated by a factor of 25-100 percent depending on the system that is being used. In the system with 100 percent acceleration (goldfish optic axons), intra-axonal protein transport is altered in a specific manner following the testing lesion: the fast component shows an early, modest, and transient increase, whereas, the slow component shows an early, marked, and sustained increase. Since the slow component uniquely conveys the cytoskeletal proteins of the axon (actin, tubulin, neuroofilament proteins, microtublle-associated proteins, and actin-associated proteins0, normal axonal outgrowth is apparently dependent on a dynamic, although sub-optimal, organization of cytoskeletal proteins; when the neuron has been conditioned for growth, the organization becomes optimal. In order to better define this organization, and the changes that occur in it during accelerated outgrowth, the proposed experiments will define the concentrations, relative enrichments, and long term associations of 35S-methionine labeled cytoskeletal proteins as they enter newly-formed daughter axons in vivo. Candidates for the most important changes will be those conserved during vertebrate evolution, that is, are found to occur in both regenerating goldfish optic axons and regenerating rat sciatic motor axons. The long-term objective of these studies that combine cell biology and experimental neurology is to identify the cytoskeletal protein interactions that govern the rate and competitive vigor (vs. environmental obstructions such as scar tissues) of axonal outgrowth. This kind of analysis will ultimately lead to an understanding of these interactions, and then to their pharmacological control. Assuming that similar progress is made in controlling the problems relating to the axonal environment, it is reasonable to anticipate the possibility that axonal regeneration can be successfully stimulated in selected patients who have sustained an incapacitating injury of the central nervous system.